Safety of Fluorescein Angiography During Pregnancy Lawrence S. Halperin, M.D., R. Joseph Olk, M.D., Gisele Soubrane, M.D., and Gabriel Coscas, M.D.
Wesent 424 retina specialists questionnaires on fluorescein angiography performed on pregnant women; 399 specialists responded. Of these, 309 (77%) had never performed fluorescein angiography on a pregnant woman. Ninety specialists (23%) had performed at least one fluorescein angiogram on a pregnant woman; detailed information was obtained on 105 patients. Authors of previous reports that included fluorescein angiography during pregnancy provided information about an additional 11 patients. Substantiated side effects were nausea or vomiting in seven patients. Anomalies at birth, an undescended testicle and syndactyly, were reported in two children. There was one stillbirth with pathologic findings classic for toxemia, and one fetal death occurred several months after fluorescein angiography. One therapeutic abortion was performed for complications in toxemia. One spontaneous abortion occurred three days after fluorescein angiography in a patient who was four weeks pregnant. Eight children born to toxemic mothers had low birth weights. We conclude that fluorescein angiography does not cause a high rate of birth anomalies or complications during pregnancy. OCCASIONALLY, a vision-threatening lesion occurs during pregnancy. If the lesion requires fluorescein angiography for either diagnosis or treatment, the question of the safety of the procedure arises. Furthermore, women may undergo fluorescein angiography before realizing they are pregnant. Although published reports
Accepted for publication March 1, 1990. From the Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri (Drs. Halperin and OIk), and Clinique Ophtalmologique Universitaire de Creteil and Universite de Paris Val Marne, Paris, France (Drs. Soubrane and Coscas). Reprint requests to R. Joseph Olk, M.D., Retina Consultants, Ltd., East Pavilion, Ste. 17413, One Barnes Hospital Plaza, St. Louis, MO 63110.
©AMmuCAN JOURNAL OF OPHTHALMOLOGY
state that fluorescein angiography should be avoided during pregnancy.!" there is little information about the safety of the procedure during pregnancy. We surveyed retina specialists to compile information on patients who had fluorescein angiography during pregnancy. All cases in which information about the health of the mother and child were available were included.
Material and Methods Four hundred twenty-four members of the Retina, Macula, and Vitreous Societies, the Paul Cibis Club, and the Club Jules Gonin were surveyed to identify those who had performed at least one fluorescein angiogram on a pregnant woman in the previous ten years. Specialists who responded affirmatively were contacted for information about each patient. Follow-up questionnaires requested maternal age, medical history, reason for fluorescein angiography, number of studies performed per patient, and the trimester the study was performed. Side effects were reported, as was any required treatment. The gestational ages of the children were requested. Fetal and neonatal as well as maternal complications were included. The brand and concentration of fluorescein were reported. Several previous reports described fluorescein angiography during pregnancy.r" If inadequate information was provided in the published case reports, the authors were contacted and asked to complete our questionnaire. Questionnaires were rejected if they lacked information on fetal, neonatal, or maternal complications.
Results A total of 424 retina specialists were surveyed and 403 (95%) responded. Three hundred thir-
109:563-566, MAy, 1990
563
S64
May, 1990
AMERICAN JOURNAL OF OPHTHALMOLOGY
teen specialists (78%) said they had not performed even one fluorescein angiography on a pregnant woman during the past ten years. Ninety (22%) had performed at least one. The 90 specialists were further questioned for information about their patients. Forty-five specialists could not provide additional information because of an inability to identify the patients who had fluorescein angiography during pregnancy. Nine specialists could not be reached for further information. Thirty-six specialists were able to provide information on 105 patients who had fluorescein angiography during pregnancy in the previous ten years. Forty six of the 105 patients had been described in previous reports H ,16; further information was obtained as required. An additional six reports added 11 patients, making the total 116. Nineteen patients underwent fluorescein angiography in the first trimester, 26 patients underwent the procedure in the second trimester, 30 patients underwent the procedure in the third trimester, and 22 patients underwent the procedure in each trimester. Seventy-one patients had one fluorescein angiogram during pregnancy, eight patients had two, 32 patients had three, and two patients had four. Diabetic retinopathy (40 patients), toxemia of pregnancy (31 patients), and choroidal neovascular membrane (27 patients) were the three most common reasons for fluorescein angiography during pregnancy. Other reasons for the procedure included central serous retinopathy (five patients), vasculitis (two patients), acute multifocal placoid pigment epitheliopathy (one patient), retinal venous occlusion (one patient), optic disk edema (one patient), multiple evanescent white dot syndrome (one patient), sickle cell retinopathy (one patient), choroidal hemangioma (one patient), intracranial hypertension (one patient), and unknown (four patients). Many of the patients with diabetes and toxemia underwent fluorescein angiography as part of a prospective clinical study rather than for diagnostic or therapeutic purposes. Three of the 116 patients had nausea as a side effect of fluorescein angiography, and four patients had both nausea and vomiting. None of the patients required treatment for these symptoms. There were no patient deaths from fluorescein angiography during pregnancy. The gestational ages of the children born to the 116 patients were as follows: greater than 34 weeks for 103 children; 28 weeks for one child; and 12 children had unknown gestational
ages. Ten diabetic patients required cesarean section. The average maternal age was 27 years. There were four neonatal or fetal deaths. These are not included in the study for the following reasons: one infant was stillborn, and the placenta had obvious pathologic indications of eclampsia; one therapeutic abortion was performed for complications of eclampsia; one fetal death occurred months after fluorescein angiography (no further information about the presence of fetal anomalies in this child was available); and one spontaneous abortion occurred three days after fluorescein angiography in a four-week pregnancy of an otherwise healthy woman. Birth anomalies were reported in two children. One child had an undescended testicle, and one child had syndactyly. Eight babies born of patients with hypertension-related pregnancies had a low birth weight. Fluorescein concentrations ranged from 10% to 25%. There was no correlation of brand, concentration, or timing of fluorescein administration with fetal deaths, fetal anomalies, or patient side effects.
Discussion
Reports about retinal disease during pregnancy have stated that fluorescein angiography was specifically avoided because of possible adverse effects."! Recent reports, however, stated that no data were available on the use of fluorescein angiography during pregnancy.l-" Reviews about side effects and complications of fluorescein angiography't-" do not include complications of fluorescein angiography during pregnancy. Yannuzzi and associates" mentioned that pregnancy is a contraindication to fluorescein angiography. Approximately 80% of the 2,434 responding ophthalmologists in their study said they would not perform fluorescein angiography on a pregnant patient. Those who would do the procedure indicated that it should be reserved for vision-threatening lesions and that the study should be performed only in the latter part of pregnancy. Package inserts for most brands of intravenous fluorescein dye state that injection should be avoided during pregnancy, especially in the first trimester. The inserts also state that no fetal complications have ever been reported from intravenous fluorescein. The incidence of nausea and vomiting report-
Fluorescein Angiography During Pregnancy
Vol. 109, No.5
ed in our study was approximately 6% (seven patients). This concurs with the data in other studies. 17-J9,23 Furthermore, other side effects such as dizziness, anaphylactoid reaction, rash, and pruritus were not described by any of the patients in this study. Birth anomalies were rare in this series of 116 patients. Many patients in this study had a higher than normal risk of fetal anomalies (diabetic patients) and fetal mortality (patients with toxemia or sickle cell anemia)." Pregnancies complicated by pregnancy-related hypertension have an increased risk of perinatal mortality and growth retardation. Pregnancyrelated hypertension accounted for many of the fetal complications described in this study. Diabetic patients have an increased risk of fetal death of approximately 4%, and congenital malformations occur at an increased rate. Several studies about teratogenicity of fluorescein in animals found no increased incidence of fetal anomalies or deaths when intravenous fluorescein was given in standard doses during early stages of pregnancy.P" One study showed that fluorescein freely crosses the placenta of rats and is found in the fetus for several hours after injection." Fluorescein also crosses the placenta in humans as is shown by the finding of fluorescein dye in amniotic fluid obtained from amniocentesis in a patient 33 weeks pregnant who had undergone fluorescein angiography several days before .13 We conclude that fluorescein angiography does not result in a high rate of birth anomalies or complications when performed on a pregnant patient. Based on our data and existing animal data, we believe it is reasonable to perform fluorescein angiography on a pregnant patient when vision is threatened by a choroidal neovascular membrane; fluorescein angiography could affect the patient's treatment or eventual outcome. The decision to perform fluorescein angiography on a pregnant patient is left to the physician and patient, who should carefully weigh the risks and benefits of the procedure. Additionally, we believe that our data can be valuable to ophthalmologists who must advise patients who underwent fluorescein angiography before they knew they were pregnant. ACKNOWLEDGMENTS
The following physicians provided the data for this study: William E. Benson, M.D.; Michael A. Bloome, M.D.; Edwin E. Boldrey, M.D.;
565
Isaac Boniuk, M.D.; Randy V. Campo, M.D.; Brian P. Conway, M.D.; Guillermo B. De Venecia, M.D.; Robert N. Frank, M.D.; M. Wallace Friedman, M.D.; Kurt A. Gitter, M.D.; Rodney Grey, F.R.C.S.; Stephen E. Grinde, M.D.; G. Robert Hampton, M.D.; Gordon S. Harris, M.D.; Vernon M. Hermsen, M.D.; Timothy Holekamp, M.D.; David O. [esberg, M.D.; Leonard Joffe, M.D.; Leila Laatikainen, M.D.; Maurice B. Landers, M.D.; Roy A. Levit, M.D.; Matthew J. Lipman, M.D.; Louis A. Lobes, M.D.; Travis A. Meredith, M.D.; Ronald G. Michels, M.D.; Peter H. Morse, M.D.; Thomas R. Pheasant, M.D.; Alvaro Rodriguez, M.D.; Ted Schlaegal, M.D.; Stephen H. Sinclair, M.D.; Thomas P. Stratford, M.D.; John J. Weiter, M.D.; and Herbert S. Woldoff, M.D.
References 1. Fastenberg, D. M., Fetkenhour, C. L., Choromokos, E., and Shoch, D. E.: Choroidal vascular changes in toxemia of pregnancy. Am. J. Ophthalmol. 89:362, 1980. 2. Fastenberg, D. M., and Ober, R. R.: Central serous choroidopathy in pregnancy. Arch. Ophthalmol. 101:1055,1983. 3. Folk, J. c.. and Weingeist, T. A.: Fundus changes in toxemia. Ophthalmology 88:1173, 1981. 4. Horvat, M., Maclean, H., Goldberg, L., and Crock, G. W.: Diabetic retinopathy in pregnancy. A 12-year prospective survey. Br. J. Ophthalmol. 64:398, 1980. 5. Mabie, W. c., and Ober, R. R.: Fluorescein angiography in toxemia of pregnancy. Br. J. Ophthalmol. 64:666,1980. 6. Oliver, M., and Uchenik, D.: Bilateral exudate retinal detachment in eclampsia without hypertensive retinopathy. Am. J. Ophthalmol. 90:792, 1980. 7. Samples, J. R., and Meyer, S. M.: Use of ophthalmic medications in pregnant and nursing women. Am. J. Ophthalmol. 106:616, 1988. 8. Pitta, C.; Bergen, R., and Littwin, 5.: Spontaneous regression of a choroidal hemangioma following pregnancy. Ann. Ophthalmol. 11:772, 1979. 9. Spitzberg, D. H.: Retinal phlebitis associated with pregnancy. Ann. Ophthalmol. 14:101, 1982. 10. Gitter, K. A., Houser, B. P., Sarin, L. K., and Justice, J.: Toxemia of pregnancy. Arch. Ophthalmol. 80:449, 1968. 11. Donkers, B., and [ansonius, D.: Fluorescein angiography in hypertensive pregnancies. Am. J. Obstet. Gynecol. 138:461, 1980. 12. Chumbley, L. c., and Frank, R. N.: Central serous retinopathy and pregnancy. Am. J. Ophthalmol. 77:158, 1974. 13. Shekleton, P., Fidler, J., and Grimwade, J.: A
566
AMERICAN JOURNAL OF OPHTHALMOLOGY
case of benign intracranial hypertension in pregnancy. Brit. J. Obstet. Gynecol. 87:345, 1980. 14. Soubrane, G., Canivet, J., and Coscas, G.: Influence of pregnancy on the evolution of background retinopathy. Preliminary results of a prospective fluorescein angiography study. Int. Ophthalmol. 8:249, 1985. 15. Chaine, G., Attali, P., Gaudric, A., Colin, M., Quentel, G., and Coscas, G.: Ocular fluorophotornetric and angiographic findings in toxemia of pregnancy. Arch. Ophthalmol. 104:1632, 1986. 16. Sunness, J. S.: The pregnant woman's eye. Surv. Ophthalmol. 32:219, 1988. 17. Butner, R. W., and McPherson, A. R.: Adverse reactions in intravenous fluorescein angiography. Ann. Ophthalmol. 15:1084, 1983. 18. Pacurariu, R. 1.: Low incidence of side effects following intravenous fluorescein angiography. Ann. Ophthalmol. 14:32, 1982. 19. Karhunen, U., Raitta, c.. and Kala, R.: Adverse reactions of fluorescein angiography. Acta Ophthalmol. 64:282, 1986. 20. Chazan, B. 1., Marios, M. B., Balodimos, M. c., and Koncz, L.: Untoward effects of fluorescein retinal angiography in diabetic patients. Ann. Ophthalmol. 3:42, 1971.
May, 1990
21. Marcus, D. F., Bovina, J. A., and Williams, D.: Adverse reactions during intravenous fluorescein angiography. Arch. Ophthalmol. 102:825, 1984. 22. Greene, G. S., Bell, L. W., Hitching, R. A., and Spaeth, G. L.: Adverse reaction to intravenous fluorescein. Evidence for sex differences. Ann. Ophthalmol. 8:533, 1976. 23. Yannuzzi, L. A., Roher, K. T., Tindel, L. J., Sobel, R. S., Constanza, M. A., Shields, W., and Zang, E.: Fluorescein angiography complication survey. Ophthalmology 93:611, 1986. 24. Creasy, R. K., and Resnik, R.: Maternal Fetal Medicine, ed. 2. Philadelphia, W. B. Saunders, 1989, pp. 897-899. 25. McEnerney, J. K., Wong, W. P., and Peyman, G. A.: Evaluation of the teratogenicity of fluorescein sodium. Am. J. Ophthalmol. 84:847,1977. 26. Salem, H., Loux, J. J., Smith, S., and Nichols, C. W.: Evaluation of the toxicologic and teratogenic potentials of sodium fluorescein in the rat. Toxicology 12:143, 1979. 27. Shirai, S., and Majima, A.: Effects of fluorescein sodium injected to mother mice on the embryo. Bull. [pn. Ophthalmol. 26:132, 1975.
OPHTHALMIC MINIATURE
"Yow," said Koko. He jumped to the bed and looked at the man with sympathetically blinking eyes. They were sapphire blue in bright light, but in the lamplit hotel room they were large circles of black onyx with flashes of diamond or ruby. Lilian Jackson Braun, The Cat Who Turned On and Off New York, Berkley Publishing Group, 1986, p. 6
Wesent 424 retina specialists questionnaires on fluorescein angiography performed on pregnant women; 399 specialists responded. Of these, 309 (77%) had never performed fluorescein angiography on a pregnant woman. Ninety specialists (23%) had performed at least one fluorescein angiogram on a pregnant woman; detailed information was obtained on 105 patients. Authors of previous reports that included fluorescein angiography during pregnancy provided information about an additional 11 patients. Substantiated side effects were nausea or vomiting in seven patients. Anomalies at birth, an undescended testicle and syndactyly, were reported in two children. There was one stillbirth with pathologic findings classic for toxemia, and one fetal death occurred several months after fluorescein angiography. One therapeutic abortion was performed for complications in toxemia. One spontaneous abortion occurred three days after fluorescein angiography in a patient who was four weeks pregnant. Eight children born to toxemic mothers had low birth weights. We conclude that fluorescein angiography does not cause a high rate of birth anomalies or complications during pregnancy. OCCASIONALLY, a vision-threatening lesion occurs during pregnancy. If the lesion requires fluorescein angiography for either diagnosis or treatment, the question of the safety of the procedure arises. Furthermore, women may undergo fluorescein angiography before realizing they are pregnant. Although published reports
Accepted for publication March 1, 1990. From the Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri (Drs. Halperin and OIk), and Clinique Ophtalmologique Universitaire de Creteil and Universite de Paris Val Marne, Paris, France (Drs. Soubrane and Coscas). Reprint requests to R. Joseph Olk, M.D., Retina Consultants, Ltd., East Pavilion, Ste. 17413, One Barnes Hospital Plaza, St. Louis, MO 63110.
©AMmuCAN JOURNAL OF OPHTHALMOLOGY
state that fluorescein angiography should be avoided during pregnancy.!" there is little information about the safety of the procedure during pregnancy. We surveyed retina specialists to compile information on patients who had fluorescein angiography during pregnancy. All cases in which information about the health of the mother and child were available were included.
Material and Methods Four hundred twenty-four members of the Retina, Macula, and Vitreous Societies, the Paul Cibis Club, and the Club Jules Gonin were surveyed to identify those who had performed at least one fluorescein angiogram on a pregnant woman in the previous ten years. Specialists who responded affirmatively were contacted for information about each patient. Follow-up questionnaires requested maternal age, medical history, reason for fluorescein angiography, number of studies performed per patient, and the trimester the study was performed. Side effects were reported, as was any required treatment. The gestational ages of the children were requested. Fetal and neonatal as well as maternal complications were included. The brand and concentration of fluorescein were reported. Several previous reports described fluorescein angiography during pregnancy.r" If inadequate information was provided in the published case reports, the authors were contacted and asked to complete our questionnaire. Questionnaires were rejected if they lacked information on fetal, neonatal, or maternal complications.
Results A total of 424 retina specialists were surveyed and 403 (95%) responded. Three hundred thir-
109:563-566, MAy, 1990
563
S64
May, 1990
AMERICAN JOURNAL OF OPHTHALMOLOGY
teen specialists (78%) said they had not performed even one fluorescein angiography on a pregnant woman during the past ten years. Ninety (22%) had performed at least one. The 90 specialists were further questioned for information about their patients. Forty-five specialists could not provide additional information because of an inability to identify the patients who had fluorescein angiography during pregnancy. Nine specialists could not be reached for further information. Thirty-six specialists were able to provide information on 105 patients who had fluorescein angiography during pregnancy in the previous ten years. Forty six of the 105 patients had been described in previous reports H ,16; further information was obtained as required. An additional six reports added 11 patients, making the total 116. Nineteen patients underwent fluorescein angiography in the first trimester, 26 patients underwent the procedure in the second trimester, 30 patients underwent the procedure in the third trimester, and 22 patients underwent the procedure in each trimester. Seventy-one patients had one fluorescein angiogram during pregnancy, eight patients had two, 32 patients had three, and two patients had four. Diabetic retinopathy (40 patients), toxemia of pregnancy (31 patients), and choroidal neovascular membrane (27 patients) were the three most common reasons for fluorescein angiography during pregnancy. Other reasons for the procedure included central serous retinopathy (five patients), vasculitis (two patients), acute multifocal placoid pigment epitheliopathy (one patient), retinal venous occlusion (one patient), optic disk edema (one patient), multiple evanescent white dot syndrome (one patient), sickle cell retinopathy (one patient), choroidal hemangioma (one patient), intracranial hypertension (one patient), and unknown (four patients). Many of the patients with diabetes and toxemia underwent fluorescein angiography as part of a prospective clinical study rather than for diagnostic or therapeutic purposes. Three of the 116 patients had nausea as a side effect of fluorescein angiography, and four patients had both nausea and vomiting. None of the patients required treatment for these symptoms. There were no patient deaths from fluorescein angiography during pregnancy. The gestational ages of the children born to the 116 patients were as follows: greater than 34 weeks for 103 children; 28 weeks for one child; and 12 children had unknown gestational
ages. Ten diabetic patients required cesarean section. The average maternal age was 27 years. There were four neonatal or fetal deaths. These are not included in the study for the following reasons: one infant was stillborn, and the placenta had obvious pathologic indications of eclampsia; one therapeutic abortion was performed for complications of eclampsia; one fetal death occurred months after fluorescein angiography (no further information about the presence of fetal anomalies in this child was available); and one spontaneous abortion occurred three days after fluorescein angiography in a four-week pregnancy of an otherwise healthy woman. Birth anomalies were reported in two children. One child had an undescended testicle, and one child had syndactyly. Eight babies born of patients with hypertension-related pregnancies had a low birth weight. Fluorescein concentrations ranged from 10% to 25%. There was no correlation of brand, concentration, or timing of fluorescein administration with fetal deaths, fetal anomalies, or patient side effects.
Discussion
Reports about retinal disease during pregnancy have stated that fluorescein angiography was specifically avoided because of possible adverse effects."! Recent reports, however, stated that no data were available on the use of fluorescein angiography during pregnancy.l-" Reviews about side effects and complications of fluorescein angiography't-" do not include complications of fluorescein angiography during pregnancy. Yannuzzi and associates" mentioned that pregnancy is a contraindication to fluorescein angiography. Approximately 80% of the 2,434 responding ophthalmologists in their study said they would not perform fluorescein angiography on a pregnant patient. Those who would do the procedure indicated that it should be reserved for vision-threatening lesions and that the study should be performed only in the latter part of pregnancy. Package inserts for most brands of intravenous fluorescein dye state that injection should be avoided during pregnancy, especially in the first trimester. The inserts also state that no fetal complications have ever been reported from intravenous fluorescein. The incidence of nausea and vomiting report-
Fluorescein Angiography During Pregnancy
Vol. 109, No.5
ed in our study was approximately 6% (seven patients). This concurs with the data in other studies. 17-J9,23 Furthermore, other side effects such as dizziness, anaphylactoid reaction, rash, and pruritus were not described by any of the patients in this study. Birth anomalies were rare in this series of 116 patients. Many patients in this study had a higher than normal risk of fetal anomalies (diabetic patients) and fetal mortality (patients with toxemia or sickle cell anemia)." Pregnancies complicated by pregnancy-related hypertension have an increased risk of perinatal mortality and growth retardation. Pregnancyrelated hypertension accounted for many of the fetal complications described in this study. Diabetic patients have an increased risk of fetal death of approximately 4%, and congenital malformations occur at an increased rate. Several studies about teratogenicity of fluorescein in animals found no increased incidence of fetal anomalies or deaths when intravenous fluorescein was given in standard doses during early stages of pregnancy.P" One study showed that fluorescein freely crosses the placenta of rats and is found in the fetus for several hours after injection." Fluorescein also crosses the placenta in humans as is shown by the finding of fluorescein dye in amniotic fluid obtained from amniocentesis in a patient 33 weeks pregnant who had undergone fluorescein angiography several days before .13 We conclude that fluorescein angiography does not result in a high rate of birth anomalies or complications when performed on a pregnant patient. Based on our data and existing animal data, we believe it is reasonable to perform fluorescein angiography on a pregnant patient when vision is threatened by a choroidal neovascular membrane; fluorescein angiography could affect the patient's treatment or eventual outcome. The decision to perform fluorescein angiography on a pregnant patient is left to the physician and patient, who should carefully weigh the risks and benefits of the procedure. Additionally, we believe that our data can be valuable to ophthalmologists who must advise patients who underwent fluorescein angiography before they knew they were pregnant. ACKNOWLEDGMENTS
The following physicians provided the data for this study: William E. Benson, M.D.; Michael A. Bloome, M.D.; Edwin E. Boldrey, M.D.;
565
Isaac Boniuk, M.D.; Randy V. Campo, M.D.; Brian P. Conway, M.D.; Guillermo B. De Venecia, M.D.; Robert N. Frank, M.D.; M. Wallace Friedman, M.D.; Kurt A. Gitter, M.D.; Rodney Grey, F.R.C.S.; Stephen E. Grinde, M.D.; G. Robert Hampton, M.D.; Gordon S. Harris, M.D.; Vernon M. Hermsen, M.D.; Timothy Holekamp, M.D.; David O. [esberg, M.D.; Leonard Joffe, M.D.; Leila Laatikainen, M.D.; Maurice B. Landers, M.D.; Roy A. Levit, M.D.; Matthew J. Lipman, M.D.; Louis A. Lobes, M.D.; Travis A. Meredith, M.D.; Ronald G. Michels, M.D.; Peter H. Morse, M.D.; Thomas R. Pheasant, M.D.; Alvaro Rodriguez, M.D.; Ted Schlaegal, M.D.; Stephen H. Sinclair, M.D.; Thomas P. Stratford, M.D.; John J. Weiter, M.D.; and Herbert S. Woldoff, M.D.
References 1. Fastenberg, D. M., Fetkenhour, C. L., Choromokos, E., and Shoch, D. E.: Choroidal vascular changes in toxemia of pregnancy. Am. J. Ophthalmol. 89:362, 1980. 2. Fastenberg, D. M., and Ober, R. R.: Central serous choroidopathy in pregnancy. Arch. Ophthalmol. 101:1055,1983. 3. Folk, J. c.. and Weingeist, T. A.: Fundus changes in toxemia. Ophthalmology 88:1173, 1981. 4. Horvat, M., Maclean, H., Goldberg, L., and Crock, G. W.: Diabetic retinopathy in pregnancy. A 12-year prospective survey. Br. J. Ophthalmol. 64:398, 1980. 5. Mabie, W. c., and Ober, R. R.: Fluorescein angiography in toxemia of pregnancy. Br. J. Ophthalmol. 64:666,1980. 6. Oliver, M., and Uchenik, D.: Bilateral exudate retinal detachment in eclampsia without hypertensive retinopathy. Am. J. Ophthalmol. 90:792, 1980. 7. Samples, J. R., and Meyer, S. M.: Use of ophthalmic medications in pregnant and nursing women. Am. J. Ophthalmol. 106:616, 1988. 8. Pitta, C.; Bergen, R., and Littwin, 5.: Spontaneous regression of a choroidal hemangioma following pregnancy. Ann. Ophthalmol. 11:772, 1979. 9. Spitzberg, D. H.: Retinal phlebitis associated with pregnancy. Ann. Ophthalmol. 14:101, 1982. 10. Gitter, K. A., Houser, B. P., Sarin, L. K., and Justice, J.: Toxemia of pregnancy. Arch. Ophthalmol. 80:449, 1968. 11. Donkers, B., and [ansonius, D.: Fluorescein angiography in hypertensive pregnancies. Am. J. Obstet. Gynecol. 138:461, 1980. 12. Chumbley, L. c., and Frank, R. N.: Central serous retinopathy and pregnancy. Am. J. Ophthalmol. 77:158, 1974. 13. Shekleton, P., Fidler, J., and Grimwade, J.: A
566
AMERICAN JOURNAL OF OPHTHALMOLOGY
case of benign intracranial hypertension in pregnancy. Brit. J. Obstet. Gynecol. 87:345, 1980. 14. Soubrane, G., Canivet, J., and Coscas, G.: Influence of pregnancy on the evolution of background retinopathy. Preliminary results of a prospective fluorescein angiography study. Int. Ophthalmol. 8:249, 1985. 15. Chaine, G., Attali, P., Gaudric, A., Colin, M., Quentel, G., and Coscas, G.: Ocular fluorophotornetric and angiographic findings in toxemia of pregnancy. Arch. Ophthalmol. 104:1632, 1986. 16. Sunness, J. S.: The pregnant woman's eye. Surv. Ophthalmol. 32:219, 1988. 17. Butner, R. W., and McPherson, A. R.: Adverse reactions in intravenous fluorescein angiography. Ann. Ophthalmol. 15:1084, 1983. 18. Pacurariu, R. 1.: Low incidence of side effects following intravenous fluorescein angiography. Ann. Ophthalmol. 14:32, 1982. 19. Karhunen, U., Raitta, c.. and Kala, R.: Adverse reactions of fluorescein angiography. Acta Ophthalmol. 64:282, 1986. 20. Chazan, B. 1., Marios, M. B., Balodimos, M. c., and Koncz, L.: Untoward effects of fluorescein retinal angiography in diabetic patients. Ann. Ophthalmol. 3:42, 1971.
May, 1990
21. Marcus, D. F., Bovina, J. A., and Williams, D.: Adverse reactions during intravenous fluorescein angiography. Arch. Ophthalmol. 102:825, 1984. 22. Greene, G. S., Bell, L. W., Hitching, R. A., and Spaeth, G. L.: Adverse reaction to intravenous fluorescein. Evidence for sex differences. Ann. Ophthalmol. 8:533, 1976. 23. Yannuzzi, L. A., Roher, K. T., Tindel, L. J., Sobel, R. S., Constanza, M. A., Shields, W., and Zang, E.: Fluorescein angiography complication survey. Ophthalmology 93:611, 1986. 24. Creasy, R. K., and Resnik, R.: Maternal Fetal Medicine, ed. 2. Philadelphia, W. B. Saunders, 1989, pp. 897-899. 25. McEnerney, J. K., Wong, W. P., and Peyman, G. A.: Evaluation of the teratogenicity of fluorescein sodium. Am. J. Ophthalmol. 84:847,1977. 26. Salem, H., Loux, J. J., Smith, S., and Nichols, C. W.: Evaluation of the toxicologic and teratogenic potentials of sodium fluorescein in the rat. Toxicology 12:143, 1979. 27. Shirai, S., and Majima, A.: Effects of fluorescein sodium injected to mother mice on the embryo. Bull. [pn. Ophthalmol. 26:132, 1975.
OPHTHALMIC MINIATURE
"Yow," said Koko. He jumped to the bed and looked at the man with sympathetically blinking eyes. They were sapphire blue in bright light, but in the lamplit hotel room they were large circles of black onyx with flashes of diamond or ruby. Lilian Jackson Braun, The Cat Who Turned On and Off New York, Berkley Publishing Group, 1986, p. 6
